Immunostimulatory nucleic acid oil-in-water formulations and related methods of use

Abstract

The invention involves methods and compositions of an immunostimulatory nucleic acid in oil-in-water emulsions for topical delivery. The compositions can be used to stimulate immune responses, particularly useful in the prevention and/or treatment of infectious disease and cancer.

We claim:  
     
         1 . A method for inducing an immune response, comprising: 
 topically administering to a subject an oil-in-water emulsion and an immunostimulatory nucleic acid in an effective amount to induce an immune response.    
     
     
         2 - 40 . (Cancelled)  
     
     
         41 . A composition comprising 
 an immunostimulatory nucleic acid and an oil-in-water emulsion, formulated for topical skin or mucosal delivery.    
     
     
         42 . The composition of  claim 41 , further comprising administering an antigen.  
     
     
         43 . The composition of  claim 41 , wherein the immunostimulatory nucleic acid is a CpG immunostimulatory nucleic acid.  
     
     
         44 . The composition of  claim 41 , wherein the oil-in-water emulsion and the immunostimulatory nucleic acid is administered to a mucosal surface.  
     
     
         45 . The composition of  claim 44 , wherein the mucosal surface is an oral surface, a rectal surface, a nasal surface, a vaginal surface or an ocular surface.  
     
     
         46 . The composition of  claim 41 , wherein the oil-in-water emulsion and the immunostimulatory nucleic acid is administered to a skin surface.  
     
     
         47 . The composition of  claim 41 , wherein the immunostimulatory nucleic acid is a T-rich nucleic acid.  
     
     
         48 . The composition of  claim 47 , wherein the T-rich nucleic acid has a sequence selected from the group consisting of SEQ ID NOs: 52-57 and SEQ ID NOs: 62-94.  
     
     
         49 . The composition of  claim 41 , wherein the immunostimulatory nucleic acid is a poly-G nucleic acid.  
     
     
         50 . The composition of  claim 49 , wherein the poly-G nucleic acid has a sequence selected from the group consisting of SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 58, SEQ ID NO: 61 and SEQ ID NOs: 95-133.  
     
     
         51 . The composition of  claim 41 , wherein the immunostimulatory nucleic acid has a sequence selected from the group consisting of SEQ ID NOs: 1-146.  
     
     
         52 . The composition of  claim 41 , wherein the immunostimulatory nucleic acid has a modified backbone.  
     
     
         53 . The composition of  claim 52 , wherein the modified backbone is a phosphate modified backbone.  
     
     
         54 . The composition of  claim 53 , wherein the phosphate modified backbone is a phosphorothioate modified backbone.  
     
     
         55 . The composition of  claim 53 , wherein the modified backbone is a peptide modified oligonucleotide backbone.  
     
     
         56 . The composition of  claim 41 , wherein the immunostimulatory nucleic acid has the nucleotide seqeunce of  
       
         
           
                 
                 
                 
               
                     
                 
                   TCG TCG TTT TGT CGT TTT GTC GTT, 
                   (SEQ ID NO: 147) 
                     
                 
                     
                 
                   TCG TCG TTT CGT CGT TTC GTC GTT, 
                   (SEQ ID NO: 148) 
                 
                     
                 
                   TCG TCG TTT TTC GGT CGT TTT, 
                   (SEQ ID NO: 149) 
                 
                     
                 
                   TCG TCG TTT CGT CGT TTT GTC GTT, 
                   (SEQ ID NO: 150) 
                 
                     
                 
                   TCG TCG TTT TGT CGT TTT TTT CGA 
                   (SEQ ID NO: 151) 
                 
                   or 
                 
                     
                 
                   TCG TCG TTT TTC GTG CGT TTT T. 
                   (SEQ ID NO: 152) 
                 
                     
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         57 . The composition of  claim 41 , wherein the immunostimulatory nucleic acid has the nucleotide seqeunce of  
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                   TCGTCGTTGTCGTTTTGTCGTT. 
                   (SEQ ID NO: 153) 
                 
                     
                     
                 
             
                
                
                
               
            
           
         
       
     
     
         58 . The composition of  claim 41 , wherein the immunostimulatory nucleic acid and oil-in-water emulsion is formulated for mucosal delivery.  
     
     
         59 . The composition of  claim 41 , wherein the immunostimulatory nucleic acid and oil-in-water emulsion is formulated for oral deliver, ocular delivery, nasal delivery, vaginal delivery or rectal delivery.  
     
     
         60 . The composition of  claim 41 , wherein the immunostimulatory nucleic acid and oil-in-water emulsion is formulated for skin delivery.  
     
     
         61 . The composition of  claim 41 , wherein the immunostimulatory nucleic acid is a class A immunostimulatory nucleic acid, a class C immunostimulatory nucleic acid, a semi-soft immunostimulatory nucleic acid or a soft immunostimulatory nucleic acid.